Individual contribution of PDE4B and PDE4D subfamilies to the prevention of object location memory impairments induced by sleep deprivation

Hongyu Zhao; Arjan Blokland; Jos Prickaerts; Robbert Havekes; Elroy L Meijer; Pim R.A. Heckman

doi:10.1101/lm.054101.125

Individual contribution of PDE4B and PDE4D subfamilies to the prevention of object location memory impairments induced by sleep deprivation

Hongyu Zhao
, Arjan Blokland
, Jos Prickaerts
, Robbert Havekes
, Elroy L Meijer
, Pim R.A. Heckman^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Insufficient sleep compromises the cAMP signaling pathway in the hippocampus, negatively impacting hippocampus-dependent memory. In the current study, we explored whether selective PDE4B or selective PDE4D inhibition can improve hippocampus-dependent spatial memory in the object location test (OLT) in mice after sleep deprivation (SD). The results demonstrated that SD impaired the OLT performance, and both A-33 and zatolmilast protected against the negative consequences of SD when administered at the start and middle of the SD period. These findings suggest that both PDE4B and PDE4D subfamilies contribute to the beneficial effect of PDE4 inhibition against SD-induced memory consolidation impairment.

Original language	English
Article number	a054101
Number of pages	7
Journal	Learning & Memory
Volume	32
Issue number	5-6
DOIs	https://doi.org/10.1101/lm.054101.125
Publication status	Published - May 2025

Keywords

Animals
Cyclic Nucleotide Phosphodiesterases, Type 4/metabolism
Sleep Deprivation/complications
Mice
Male
Memory Disorders/etiology prevention & control
Spatial Memory/drug effects physiology
Phosphodiesterase 4 Inhibitors/pharmacology
Cyclic Nucleotide Phosphodiesterases, Type 3/metabolism
Hippocampus/drug effects
Mice, Inbred C57BL

Access to Document

10.1101/lm.054101.125Licence: CC BY-NC

Cite this

@article{8b4da55465424f439c25e2e12c784ea8,

title = "Individual contribution of PDE4B and PDE4D subfamilies to the prevention of object location memory impairments induced by sleep deprivation",

abstract = "Insufficient sleep compromises the cAMP signaling pathway in the hippocampus, negatively impacting hippocampus-dependent memory. In the current study, we explored whether selective PDE4B or selective PDE4D inhibition can improve hippocampus-dependent spatial memory in the object location test (OLT) in mice after sleep deprivation (SD). The results demonstrated that SD impaired the OLT performance, and both A-33 and zatolmilast protected against the negative consequences of SD when administered at the start and middle of the SD period. These findings suggest that both PDE4B and PDE4D subfamilies contribute to the beneficial effect of PDE4 inhibition against SD-induced memory consolidation impairment.",

keywords = "Animals, Cyclic Nucleotide Phosphodiesterases, Type 4/metabolism, Sleep Deprivation/complications, Mice, Male, Memory Disorders/etiology prevention \& control, Spatial Memory/drug effects physiology, Phosphodiesterase 4 Inhibitors/pharmacology, Cyclic Nucleotide Phosphodiesterases, Type 3/metabolism, Hippocampus/drug effects, Mice, Inbred C57BL",

author = "Hongyu Zhao and Arjan Blokland and Jos Prickaerts and Robbert Havekes and Meijer, \{Elroy L\} and Heckman, \{Pim R.A.\}",

year = "2025",

month = may,

doi = "10.1101/lm.054101.125",

language = "English",

volume = "32",

journal = "Learning \& Memory",

issn = "1072-0502",

publisher = "Cold Spring Harbor Laboratory Press",

number = "5-6",

}

TY - JOUR

T1 - Individual contribution of PDE4B and PDE4D subfamilies to the prevention of object location memory impairments induced by sleep deprivation

AU - Zhao, Hongyu

AU - Blokland, Arjan

AU - Prickaerts, Jos

AU - Havekes, Robbert

AU - Meijer, Elroy L

AU - Heckman, Pim R.A.

PY - 2025/5

Y1 - 2025/5

N2 - Insufficient sleep compromises the cAMP signaling pathway in the hippocampus, negatively impacting hippocampus-dependent memory. In the current study, we explored whether selective PDE4B or selective PDE4D inhibition can improve hippocampus-dependent spatial memory in the object location test (OLT) in mice after sleep deprivation (SD). The results demonstrated that SD impaired the OLT performance, and both A-33 and zatolmilast protected against the negative consequences of SD when administered at the start and middle of the SD period. These findings suggest that both PDE4B and PDE4D subfamilies contribute to the beneficial effect of PDE4 inhibition against SD-induced memory consolidation impairment.

AB - Insufficient sleep compromises the cAMP signaling pathway in the hippocampus, negatively impacting hippocampus-dependent memory. In the current study, we explored whether selective PDE4B or selective PDE4D inhibition can improve hippocampus-dependent spatial memory in the object location test (OLT) in mice after sleep deprivation (SD). The results demonstrated that SD impaired the OLT performance, and both A-33 and zatolmilast protected against the negative consequences of SD when administered at the start and middle of the SD period. These findings suggest that both PDE4B and PDE4D subfamilies contribute to the beneficial effect of PDE4 inhibition against SD-induced memory consolidation impairment.

KW - Animals

KW - Cyclic Nucleotide Phosphodiesterases, Type 4/metabolism

KW - Sleep Deprivation/complications

KW - Mice

KW - Male

KW - Memory Disorders/etiology prevention & control

KW - Spatial Memory/drug effects physiology

KW - Phosphodiesterase 4 Inhibitors/pharmacology

KW - Cyclic Nucleotide Phosphodiesterases, Type 3/metabolism

KW - Hippocampus/drug effects

KW - Mice, Inbred C57BL

U2 - 10.1101/lm.054101.125

DO - 10.1101/lm.054101.125

M3 - Article

SN - 1072-0502

VL - 32

JO - Learning & Memory

JF - Learning & Memory

IS - 5-6

M1 - a054101

ER -

Individual contribution of PDE4B and PDE4D subfamilies to the prevention of object location memory impairments induced by sleep deprivation

Abstract

Keywords

Access to Document

Fingerprint

Cite this